Efavirenz + AZT/3TC: 36 week Update

 

Week 24 data of this study was reported at Geneva and week 36 data was reported at ICAAC. As well, several additional studies of efavirenz were reported at ICAAC. They included EFV+indinavir, EFV+nelfinavir, and a late-breaker of efavirenz+nelfinavir in children. This report will present the 36 week EFV/AZT/3TC data and the other studies will be reviewed in following reports.

 

It was reported that EFV --

 

This study (protocool #006) compared EFV+AZT/3TC to EFV+indinavir and Indinavir+AZT/3TC. Participants were required to be PI, NNRTI and 3TC naive, and have >10,000 copies/ml and >50 CD4. 85% were treatment naive; 60% were caucasian, 17% black, and 19% hispanic; 86% were male. There was no statistical differences in demographics between the 3 treatment arms. The mean baseline CD4 and viral load were about the same for each arm--overall mean-345 CD4, 58,884 copies/ml.

 

Due to new FDA review procedures studies are now being statistically analyzed by 3 different methods. This is confusing but I'll try to define each clearly. Making it more difficult is that sometimes a company will define their as-observed or intent-to-treat analysis differently than another company. In each instance I will try to explain their definitions.

 

 

Viral Load Results at Week 36 only for the EFV+AZT/3TC Treatment Arm

 

 

Ultrasensitive Viral Load Data at Week 36 for EFV+AZT/3TC arm only

 

 

At week 24, 76% were reported to have <50 copies/ml using the on-treatment analysis. The difference between 88% and 76% may not be statistically significant.

 

The mean CD4 increase was about 180 at week 36.

 

Premature Terminations at 36 Weeks

 Reason

 EFV+AZT+3TC

 EFV+IDV

 IDV+AZT+3TC

 

 

 

 

 TOTAL

 25%

 30%

 41%

 Adverse Experiences

 6%

 5%

 19%

 Death

 0

 <1%

 0%

 Protocol Violation

 3%

 7%

 6%

 Withdrew Consent

 10%

 11%

 11%

 Lack of Effect/Tx Failure

 1%

 1%

 <1%

 Randomized, but not dosed

 4%

 5%

 4%

 other

 0

 <1%

 0%

AEs Leading to Discontinuation

 EFV+AZT+3TC

 (10/154)

 EFV+IDV

 (9/148)

 IDV+AZT+3TC

(28/148) 

 nervous system

 3

 nervous system

3

 gastrointestinal

15

 gastrointestinal

2

 rash

3

 nephrolithiasis

4

 Rash

1

 AST & ALT

1

  anemia

3

 other

4

 other

2

 other

6

Summary of New-Onset of Rashes

 

 EFV+AZT+3TC

 EFV+IDV

 IDV+AZT+3TC

 TOTAL

  29%

 34%

 16%

Maximum Severity      

grades 1 & 2

 29%

 32%

 16%

 grade 3

 0%

 2%

 0%

 grade 4

 0%

 0%

 0%

 % requiring disct of EFV for rash

 1%

 2%

 -

Summary of Nervous System Symptoms

 

 EFV+AZT+3TC

 EFV+IDV

 IDV+AZT+3TC

 TOTAL

 55%

 49%

 24%

Maximum Severity      

 Mild/Moderate

 51%

 48%

 24%

 Severe

 4%

1%

 0

 Maximal

 0

0

0

 % discontinuing EFV

 2%

 1%

-